The broad term, anesthesia, produced by general anesthetics, is traditionally defined as amnesia, analgesia and losses of consciousness and reflex activity. Mechanisms of anesthesia, despite many theories, remain largely unknown. In the recent clinical practice of anesthesiology, the use of high dose narcotic "anesthesia", a state of profound analgesia, is common, particularly in patients with compromised cardiovascular status. The analgesia produced by narcotics is mediated by opiate receptors present in the central nervous system. A series of endogenous opioid peptides have also been found in the central nervous system which are endogenous ligands for opiate receptors and these probably mediate certain forms of analgesia. A body of indirect pharmacological evidence indicates certain similarities between the analgesia produced by narcotics and the analgesia produced by general anesthetics, suggesting that the opiate receptor-endogenous opioid peptide system may be involved in the mediation of anesthetic-induced analgesia. In order to further characterize possible interactions between general anesthetics and the opiate receptor-endogenous opioid peptide system, the effects of anesthetics on the kinetics of opiate receptor subtypes mu, kappa and delta receptors will be studied using Scatchard analysis of radioligand binding assays selective for receptor subtype. The analgesic effects of general anesthetics will be assessed using classical tests in animals which have had their opiate receptors blocked irreversibly by drug treatment and compared with the analgesia produced in untreated animals. The concentration of endogenous opioid peptides present in cerebrospinal fluid and brain tissue samples will be measured using gel filtration and reversed-phase high performance liquid chromatography for peptide separation and radioimmunoassay for quantitation. Such samples will be obtained from animals both in the awake state and during exposure to anesthetic agents and the concentrations of endogenous opioid peptides compared. Results of the proposed studies will begin to provide answers to the question of how large a role analgesia plays in the term "anesthesia", and will not only broaden our understanding of mechanisms of anesthesia, but may result in more judicious choice of anesthetic agents in a patient care setting.